Antibody Structure
Antibodies exist in millions of different forms, each of which has a unique binding site for an antigen. The simplest antibodies are described as Y-shaped molecules with two identical antigen-binding sites, one located at the tip of each of the two arms of the Y (FIG. 1). Thus, antibodies are bivalent ligands capable of crosslinking function.
An antibody molecule is an assembly of four polypeptide chains: two identical light chains and two identical heavy chains, which are held together by disulfide bonds. There are five classes of antibodies, collectively referred to as immunoglobulins (Igs): IgA, IgD, IgE, IgG and IgM. Each class has a distinctive heavy chain which is responsible for the distinctive properties of the class. The heavy chains for the immunoglobulins in these five classes are, respectively, alpha, delta, epsilon, gamma and mu.
In addition to the five classes of heavy chains, there are two types of light chains: kappa and lambda. Either of these two types of light chains can be associated with any type of heavy chain. However, individual antibody molecules always have two identical light chains and two identical heavy chains. As a result, their antigen-binding sites are also identical.
Both the light and the heavy chains have distinct constant and variable regions. That is, they have distinct regions in which the amino acid sequences are the same or differ only slightly (the constant regions) and distinct regions in which the sequences are extremely variable (the variable regions). The variable region is located at the amino terminal portion of both the light and the heavy chains; the constant region is located at the carboxyl terminal portion of both types of chains. The variable region of the heavy chain (V.sub.H) and the variable region of the light chain (V.sub.L) associate to form the antigen-binding complexes.
The diversity of antigen binding sites is based on the variability of the amino acid sequences in those regions. However, it does not appear that the entire V.sub.L and V.sub.H regions contribute to the specificity of the antigen-binding site. Rather, each chain has three relatively small hypervariable regions, to which most of the variability in the variable regions is actually restricted. These three hypervariable regions define or form the binding site of antibodies and may consist of only 20 to 30 amino acids in the variable regions of each chain. The amino acid sequences of the rest of the variable region are relatively constant and form what is known as framework regions.
As indicated, both the light and the heavy chains have constant regions. However, the amino acid sequence in the constant region of heavy chains is approximately three times as long as the constant region sequence in light chains. It appears that a light chain has a single constant domain (C.sub.L) and most heavy chains have three separate constant domains (C.sub.H1, C.sub.H2, C.sub.H3). The epsilon and the mu chains apparently have four constant domains. The three (or four) constant domains of the heavy chain show considerable homology to each other and also to the light chain constant regions. The heavy chain constant domains (except C.sub.H1) make up the F.sub.C region, which determines the antibody's other biological characteristics.